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Title: Differential gene expression pattern in human mammary epithelial cells induced by realistic organochlorine mixtures described in healthy women and in women diagnosed with breast cancer
Authors: Figueroa Rivero, Javier 
Henríquez-Hernández, Luis Alberto 
Luzardo, Octavio P. 
Pestano, José 
Zumbado, Manuel 
Boada, Luis D. 
Valerón, Pilar F. 
UNESCO Clasification: 3214 Toxicología
320101 Oncología
Keywords: Breast cancer
Gene expression
Organochlorine mixtures
Issue Date: 2016
Journal: Toxicology Letters 
Abstract: Organochlorine pesticides (OCs) have been associated with breast cancer development and progression, but the mechanisms underlying this phenomenon are not well known. In this work, we evaluated the effects exerted on normal human mammary epithelial cells (HMEC) by the OC mixtures most frequently detected in healthy women (H-mixture) and in women diagnosed with breast cancer (BC-mixture), as identified in a previous case-control study developed in Spain. Cytotoxicity and gene expression profile of human kinases (= 68) and non-kinases (= 26) were tested at concentrations similar to those described in the serum of those cases and controls. Although both mixtures caused a down-regulation of genes involved in the ATP binding process, our results clearly indicate that both mixtures may exert a very different effect on the gene expression profile of HMEC. Thus, while BC-mixture up-regulated the expression of oncogenes associated to breast cancer (GFRA1 and BHLHB8), the H-mixture down-regulated the expression of tumor suppressor genes (EPHA4 and EPHB2). Our results indicate that the composition of the OC mixture could play a role in the initiation processes of breast cancer. In addition, the present results suggest that subtle changes in the composition and levels of pollutants involved in environmentally relevant mixtures might induce very different biological effects, which explain, at least partially, why some mixtures seem to be more carcinogenic than others. Nonetheless, our findings confirm that environmentally relevant pollutants may modulate the expression of genes closely related to carcinogenic processes in the breast, reinforcing the role exerted by environment in the regulation of genes involved in breast carcinogenesis.
ISSN: 0378-4274
DOI: 10.1016/j.toxlet.2016.02.003
Source: Toxicology Letters[ISSN 0378-4274],v. 246, p. 42-48
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